The processes of cell adhesion and migration, as well as specific morphogenetic events, underlie normal and abnormal embryonic and fetal development. Specific molecules that mediate these processes and the molecules that regulate their functions are being identified and characterized. Fibronectin and related molecules appear to be centrally involved in normal morphogenesis, e.g. in somite segmentation and neural crest cell migration. Key regions of fibronectin involved in cell adhesion were characterized by site-directed mutagenesis, monoclonal antibody dissection, and synthetic peptide inhibitors. Besides the Arg- Gly-Asp adhesive recognition sequence, two other polypeptide regions were needed to mediate effective cell adhesion. Such synergistic sequences were also necessary for fibronectin-mediated cell migration and for successful assembly of an extracellular fibronectin matrix. A distinct region of fibronectin involved in cell-type specific adhesion was characterized as Leu-Asp-Val. Type XII collagen was completely sequenced and was found to contain an Arg-Gly-Asp site plus characteristic fibronectin-tenascin family sequences. Comparative functional analyses of such related cell-interaction molecules and intermolecular chimeras will be used to define further the mechanisms of cell adhesion and migration. Mechanisms of action of molecules regulating migration and morphogenesis will also be nvestigated in detail.